Chemokines in host-protozoan-parasite interactions

Here, we review the interactions between parasites and chemokines and chemokine receptors in toxoplasmosis, trypanosomiasis, leishmaniasis, malaria and other diseases caused by protozoan parasites. The potential roles of chemokines after infection by these intracellular pathogens include host defence functions such as leukocyte recruitment, participation in cell-mediated immunity and antiprotozoal activity. However, these interactions can also help the parasite in, for example, the penetration of host cells.     

Genetics of host-parasite interactions

The evolution of host susceptibility or resistance to parasites has important consequences for the evolution of parasite virulence, host sexual selection, population dynamics of both host and parasite populations, and programs of biological control. The general observation of a fraction of Individuals within a population that is not parasitized, and/or the variability in parasite intensity among hosts, may reflect several phenomena acting at different levels of ecological organization. Yet, host-parasite coevolution requires host susceptibility and parasite virulence to be genetically variable. In spite of evolutionary and epidemiological implications of genetic heterogeneities in host-parasite systems, evidence concerning natural populations is still scarce. Here, we wish to emphasize why we need a better knowledge of the genetics of host-parasite interaction in natural populations and to review the evidence concerning the heritability of host susceptibility or resistance to parasites in natural populations of animals.     

Micro-autoradiographic studies on host-parasite interactions

Tritium labeled uredospores of Uromyces phaseoli were produced be feeding the host, Phaseolus vulgaris, with ³H-orotic acid. These spores were allowed to germinate on and to penetrate into a bean leaf. 24 hrs after inoculation, the bean rust had formed the first haustorium. All fungal structures, including the fungus walls, were heavily labeled. No label could be detected in the cells that had come into contact with the hyphae. In the infected host cell, the haustorium was labeled heavily, but the sheath around the haustorium and the host cell remained free of label. These results indicate that no detectable amounts of label leach from the bean rust into the host at this stage of infection although it is known that the rust takes up many metabolites. Since the sheath remains free of label and all fungal structures are evenly labeled, it is concluded that the sheath is formed by the host.     

Heterogeneous interspecific interactions in a host-parasite system

Macroparasites of vertebrates usually occur in multi-species communities, producing infections whose outcome in individual hosts or host populations may depend on the dynamics of interactions amongst the different component species. Within a single co-infection, competition can occur between conspecific and heterospecific parasite individuals, either directly or via the host's physiological and immune responses. We studied a natural single-host, multi-parasite model infection system (polystomes in the anuran Xenopus laevis victorianus) in which the parasite species show total interspecific competitive exclusion as adults in host individuals. Multi-species infection experiments indicated that competitive outcomes were dependent on infection species composition and strongly influenced by the intraspecific genetic identity of the interacting organisms. Our results also demonstrate the special importance of temporal heterogeneity (the sequence of infection by different species) in competition and co-existence between parasite species and predict that developmental plasticity in inferior competitors, and the induction of species-specific host resistance, will partition the within-host-individual habitat over time. We emphasise that such local (within-host) context-dependent processes are likely to be a fundamental determinant of population dynamics in multi-species parasite assemblages.     

Stability of genetic polymorphism in host-parasite interactions

Allelic diversity is common at host loci involved in parasite recognition, such as the major histocompatibility complex in vertebrates or gene-for-gene relationships in plants, and in corresponding loci encoding antigenic molecules in parasites. Diverse factors have been proposed in models to account for genetic polymorphism in host-parasite recognition. Here, a simple but general theory of host-parasite coevolution is developed. Coevolution implies the existence of indirect frequency-dependent selection (FDS), because natural selection on the host depends on the frequency of a parasite gene, and vice versa. It is shown that polymorphism can be maintained in both organisms only if there is negative, direct FDS, such that the strength of natural selection for the host resistance allele, the parasite virulence allele or both declines with increasing frequency of that allele itself. This condition may be fulfilled if the parasite has more than one generation in the same host individual, a feature which is common to most diseases. It is argued that the general theory encompasses almost all factors previously proposed to account for polymorphism at corresponding host and parasite loci, including those controlling gene-for-gene interactions.     

Helminth C-type lectins and host-parasite interactions

C-type lectins (C-TLs) are a family of carbohydrate-binding proteins intimately involved in diverse processes including vertebrate immune cell signalling and trafficking, activation of innate immunity in both vertebrates and invertebrates, and venom-induced haemostasis. Helminth C-TLs sharing sequence and structural similarity with mammalian immune cell lectins have recently been identified from nematode parasites, suggesting clear roles for these proteins at the host-parasite interface, notably in immune evasion. Here, Alex Loukas and Rick Maizels review the status of helminth lectin research and suggest ways in which parasitic worms might utilize C-TLs during their life history.     

Leishmania donovani flagellum-specific epitopes mediating host-parasite interactions

Abstract Monoclonal antibodies were developed against flagellar components of promastigotes of Leishmania donovani . The monoclonal antibody produced by clone A₁₁ (mAb A₁₁) recognised epitopes in the polypeptides with molecular weights of 86, 66 and weakly 53 kDa. These epitopes were found to be distributed along the flagellum and at the anterior end of promastigotes. The mAb A₁₁ of IgG₁ isotype strongly agglutinated the promastigotes of L. donovani . The prior treatment of promastigotes of L. donovani with mAb A₁₁ resulted in a significant ( P < 0.001) reduction in the attachment of promastigotes to cultured mouse peritoneal macrophages of line J774G8. The affinity-purified epitopes identified by mAb A₁₁ were recognised by human sera of cases of visceral leishmaniasis. The present study suggest that flagellar-specific epitopes mediate host-parasite interactions and, therefore, the role of these epitopes in the disease process is speculated.     

Population dynamics of host-parasite interactions in a cockroach-oxyuroid system

Host-parasite interactions of an urban cockroach, Blattella germanica , and its oxyuroid parasite, Blatticola blattae , were investigated. Life history data of host and parasites were collected under laboratory conditions. These data were used to model the effect of the parasite on the population dynamics of the host in order to understand the parasite's impact on the host population. The aggregation of parasites within a host was under-dispersed. Hosts normally were found to be infected with only one male and one female and rarely two or three. However, the primary sex ratio after hatching was 1.1 (males/females). Female parasite longevity equalled the life span of its host. B. blattae had a significant impact on the survival rate of the cockroach larvae and their time to reach maturity, but no effect on the survival rate of the adults. Infected host females produced fewer first oothecae than uninfected ones. Using the population parameters a simple model was developed to estimate the parasite's effect on the population dynamics of its host. According to the model the parasite suppresses the cockroach populations by ca 11%. Hence, the effect of the parasite does not appear strong enough to be used as a biological control agent by itself.     

Oxidative stress in malaria parasite-infected erythrocytes: host-parasite interactions

Experimenta naturae, like the glucose-6-phosphate dehydrogenase deficiency, indicate that malaria parasites are highly susceptible to alterations in the redox equilibrium. This offers a great potential for the development of urgently required novel chemotherapeutic strategies. However, the relationship between the redox status of malarial parasites and that of their host is complex. In this review article we summarise the presently available knowledge on sources and detoxification pathways of reactive oxygen species in malaria parasite-infected red cells, on clinical aspects of redox metabolism and redox-related mechanisms of drug action as well as future prospects for drug development. As delineated below, alterations in redox status contribute to disease manifestation including sequestration, cerebral pathology, anaemia, respiratory distress, and placental malaria. Studying haemoglobinopathies, like thalassemias and sickle cell disease, and other red cell defects that provide protection against malaria allows insights into this fine balance of redox interactions. The host immune response to malaria involves phagocytosis as well as the production of nitric oxide and oxygen radicals that form part of the host defence system and also contribute to the pathology of the disease. Haemoglobin degradation by the malarial parasite produces the redox active by-products, free haem and H(2)O(2), conferring oxidative insult on the host cell. However, the parasite also supplies antioxidant moieties to the host and possesses an efficient enzymatic antioxidant defence system including glutathione- and thioredoxin-dependent proteins. Mechanistic and structural work on these enzymes might provide a basis for targeting the parasite. Indeed, a number of currently used drugs, especially the endoperoxide antimalarials, appear to act by increasing oxidant stress, and novel drugs such as peroxidic compounds and anthroquinones are being developed.     

Evolution of cyclic sexual reproduction under host-parasite interactions

Alternate changes of sexual and asexual generations was studied theoretically by numerical analyses, from the viewpoint of host-parasite infective interactions. The host species was considered a diploid organism, characterized by two loci determining parasite resistance type and sexual strategy, between which a linkage exists to a certain degree. The sexual reproductive strategy was assumed to be determined by three alleles: asexual, complete sexual and cyclic sexual alleles. The effect of the parasites was represented by decreasing fitness functions of each host-type frequency. Numerical analyses of various linkages between genes and frequency dependence of host fitness revealed that the dynamics varied depending on whether the cyclic sexual allele was dominant or recessive against the complete sexual allele. When the cyclic sexual allele was dominant, the cyclic sexual strain persisted under intermediate frequency dependence of host fitness. On the other hand, when the cyclic sexual allele was recessive, it always tended to spread and to be maintained in the population. In such situations, both complete and cyclic sexual strains coexist, but the asexual strain is lost.     

Heads or tails: host-parasite interactions in the Drosophila-Wolbachia system

Wolbachia strains are endosymbiotic bacteria typically found in the reproductive tracts of arthropods. These bacteria manipulate host reproduction to ensure maternal transmission. They are usually transmitted vertically, so it has been predicted that they have evolved a mechanism to target the host's germ cells during development. Through cytological analysis we found that Wolbachia strains display various affinities for the germ line of Drosophila. Different Wolbachia strains show posterior, anterior, or cortical localization in Drosophila embryos, and this localization is congruent with the classification of the organisms based on the wsp (Wolbachia surface protein) gene sequence. This embryonic distribution pattern is established during early oogenesis and does not change until late stages of embryogenesis. The posterior and anterior localization of Wolbachia resembles that of oskar and bicoid mRNAs, respectively, which define the anterior-posterior axis in the Drosophila oocyte. By comparing the properties of a single Wolbachia strain in different host backgrounds and the properties of different Wolbachia strains in the same host background, we concluded that bacterial factors determine distribution, while bacterial density seems to be limited by the host. Possible implications concerning cytoplasmic incompatibility and evolution of strains are discussed.     

Molecular crosstalk in host-parasite relationships: schistosome- and leech-host interactions

The host-parasite relationship is based on subtle interplay between parasite survival strategies and host defense mechanisms. In this context, parasites often use the same or similar immune signaling molecules and/or molecular mimicry to escape host immunosurveillance. Both processes represent an adaptive strategy to ensure host immunocompatibility. This bidirectional communication between parasites and their hosts includes the renin-angiotensin, opioid and opiate systems. Here, Michel Salzet, André Capron and George Stefano review recent work on the interaction of common signaling mechanisms in schistosomes, leeches and their host.     

Parasite immune escape: new views into host-parasite interactions

For parasites of humans and animals that rely on vectors or on sexual contact for transmission, it is particularly important that infection does not to terminate before the occurrence of the crucial event that completes its lifecycle (e.g. another mosquito bite). For chronic infection to occur, it is essential that the parasite avoids clearance by the host immune system. Much progress has been made in elucidating the immunological interactions and the molecular mechanisms involved in the process of immune evasion. Mathematical models have also been invaluable in understanding these processes, particularly in the generation of new ideas about a complex form of immune evasion known as antigenic variation whereby a major target of the host immune response is varied during the course of a single infection to avoid recognition.     

Visceral leishmaniasis in eastern Sudan: parasite identification in humans and dogs; host-parasite relationships

In 1996, an epidemic outbreak of visceral leishmaniasis (VL) started in Barbar el Fugara, a village in Gedarif State (eastern Sudan). From 1997 to 2000, regular epidemiological studies were carried out in the human population, as well as in mammals and sand flies. In symptomatic patients, 46/69 lymph node, 6/20 post kala-azar dermal leishmaniasis (PKDL) and 1/4 cutaneous cultures in NNN medium were positive. In 69 dogs, 23/79 lymph node cultures were positive. In other mammals (47 rodents, five donkeys, one mongoose and one monkey) spleen and/or blood cultures were negative. Characterization of isolated strains (by starch gel electrophoresis and isoelectrofocusing) identified three zymodemes of Leishmania donovani, two of L. infantum and two of L. archibaldi complexes from patient samples and three zymodemes of L. donovani, three of L. infantum and two of L. archibaldi complexes from dog samples. Five of them were present in both man and dog. For the first time, a strain from a PKDL case was identified as L. infantum, and a child had the same L. infantum zymodeme in VL and in subsequent PKDL. Blood samples from dogs were studied by immunofluorescent antibody test (IFAT). The seroprevalence in dogs was 72.5%, 74.3% and 42.9% in 1998, 1999 and 2000, respectively. By using CDC miniature light traps 12 745 sand flies were collected and then identified. Phlebotomus papatasi (7%) and P. orientalis (5%) were sympatric, mainly inside homes (85% and 75%, respectively). These results, the relative stability of seroprevalence in dogs and the intradomiciliar presence of P. orientalis, known as a vector of VL in Sudan, suggest several hypotheses: (i) man is responsible for the disease in dogs, (ii) the dog is the reservoir of VL, (iii) the dog is an intermediate host between a possible sylvatic cycle and the anthroponotic cycle. More extensive studies are needed to assess the transmission cycle of VL in this area of Sudan.